Given the high incidence of bone trauma, cancer, and adult and congenital disease, which is associated with over 500,000 bone graft procedures each year in North America, it is not surprising that bone is the most common transplanted tissue, second only to blood. In addition to traditional bone grafting for defects, there are numerous clinical applications that can benefit from bone regeneration therapies including temporomandibular joint reconstruction to alleviate jaw pain which affects an estimated 90 million Americans, and restoration of contour and shape within reconstructed craniofacial bone. Mesenchymal stem and progenitor cells (MSPCs) are believed to play an important role during bone regeneration, however very little is known regarding their invasion into damaged or diseased tissue. To date there are no studies that examine the temporal and spatial distribution of endogenous mesenchymal stem and progenitor cells (MSPCs) during endosseous wound regeneration. Such characterization may be critical to developing therapeutic strategies that rely on recruitment of these cells (i.e., via delivery of growth factors) or the use of an exogenous source of stem or progenitor cells. Additionally, the impact of implanting or injecting scaffolds or hydrogel matrices on the migration and differentiation of MSPCs is unknown. Here we aim to characterize the spatial-temporal profile of endogenous MSPC migration and differentiation within defects that regenerate at different rates that will facilitate the creation of a core animal model for our laboratory. This will be used to interrogate various pathways involving MSPCs in regeneration of damaged or diseased bone tissue. AIM 1: To characterize the spatial and temporal aspects of MSPC migration and differentiation during endosseous wound healing within non-critical size defects. This will be accomplished through first validating antibodies in vitro with purified populations of MSPCs, followed by immunohistochemical analysis of MSPC migration and differentiation within a rat non-critical sized endosseous defect. AIM 2: To determine if the spatial-temporal migration and differentiation of endogenous MSPCs changes upon implantation of biomaterial matrices which significantly delay bone regeneration. Public Health Relevance: Existing clinical strategies for regeneration of craniofacial bone defects including functional deficits and severe aesthetic deformities are fraught with many limitations. We aim to characterize the spatial-temporal profile of endogenous mesenchymal stem and progenitor cell migration and differentiation within defects that regenerate at different rates. This will facilitate the creation of a core animal model that we can use to develop new strategies for enhancing bone regeneration based on harnessing the regenerative capacity of mesenchymal stem cells.